Method and Apparatus for Skin Resurfacing

ABSTRACT

Exemplary embodiments of method and apparatus are provided for resurfacing of skin that includes formation of a plurality of small holes, e.g., having widths less than about 1 mm or 0.5 mm, using a mechanical apparatus, thus avoiding generation of thermal damage as occurs with conventional laser resurfacing procedures and devices. The holes formed can be well-tolerated by the skin, and can exhibit shorter healing times and less swelling than conventional resurfacing procedures. The apparatus includes one or more needles adapted to remove a small portion of tissue when inserted into and withdrawn from the skin. The fractional surface coverage of the holes can be between about 0.1 and 0.7, or between about 0.2 and 0.5. The exemplary method and apparatus can produce cosmetic effects such as increases in collagen content, epidermal thickness, and dermal/epidermal junction undulations in the skin.

CROSS REFERENCE TO RELATED APPLICATION

The present application relates to and claims priority from U.S.Provisional Patent Application Ser. No. 61/437,486 filed Jan. 28, 2011,the disclosure of which is incorporated herein by reference in itsentirety.

FIELD OF THE PRESENT INVENTION

The present invention relates to cosmetic methods and apparatus formechanically generating a plurality of small damaged regions inbiological tissue, e.g., in skin or the like, which may providebeneficial cosmetic effects such as skin resurfacing and rejuvenation.

BACKGROUND INFORMATION

Skin loses its tone and smooth texture as it ages, commonly developingwrinkles and laxity. This can be further compounded by photodamage andother effects such as, e.g., scarring from acne or trauma, age-relatedrhytides, and striae. Aged skin is characterized by a flatteneddermal-epidermal junction, thinning epidermis and dermis, less fibrouscollagen, and alterations in elastin organization. Skin rejuvenationtherapies can work to remove these damaged tissues and/or and stimulatethe growth of new, healthy collagen, elastic fibers and skin cells andthereby improve the appearance of the skin.

A common procedure for skin rejuvenation, laser resurfacing, uses lightenergy to heat and damage the upper dermis. However, laser resurfacinghas a poor side effect profile, with many patients experiencingprolonged erythema, scarring and dyspigmentation. Recently, thedevelopment and use of fractional ablative therapy has achieved betterresults. A fractional damage can include forming small regions of damagein tissue (e.g., ablation or thermal damage) that are surrounded byhealthy tissue. A small size of the damaged regions (e.g., generallyless than about 1 mm) and proximity of healthy tissue can facilitate arapid healing of the damaged regions, as well as other desirable effectssuch as tissue shrinkage.

Laser-based fractional resurfacing techniques and devices involve theuse of expensive and potentially dangerous lasers or other sources ofintense optical energy to damaged tissue. Such optical systems can beexpensive, present safety hazards, and require a skilled physician orclinician for their operation.

Percutaneous collagen induction therapy (PCI), another approach formechanically inducing cosmetic improvements in skin tissue, is based onthe use of stamps or rollers to insert small solid needles through theepidermis and into the dermis of the skin to stimulate collagen growth.This technique can improve the appearance, e.g., of acne, burn scars andstriae without removal of tissue, and may provide an improved sideeffect profile, but generally has exhibited limited clinical efficacy.Because PCI does not heat the skin, needling devices also avoid theerythema and scaring that may be associated with laser treatment, andhave significantly less recovery time.

Accordingly, there may be a need for a relatively simple, inexpensive,and safe cosmetic method and device that can be mechanical in nature andwould overcome at least some of such exemplary deficiencies, and can beconfigured to produce fractional damage in biological tissue that iswell-tolerated.

SUMMARY OF EXEMPLARY EMBODIMENTS

The present invention relates to exemplary embodiments of simple,inexpensive, and safe methods and devices for mechanical generation of aplurality of small regions of damage in biological tissue, such as skin.Such exemplary damaged regions can have a size that is, e.g., about 1 mmor less as measured in at least one direction along the tissue surface.

An exemplary embodiment of an apparatus according to the presentinvention can be provided that includes one or more needles configuredto be inserted into and withdrawn from the tissue to remove portions oftissue and thereby generate damaged regions. The exemplary needles canbe hollow (e.g., coring needles) or solid, and adapted and/or sized toremove small portions of tissue when inserted into and withdrawn fromthe tissue. One or more extensions can be provided along an outersurface of the needles and/or an inner surface of the hollow needles toaffect the amount, shape, and/or characteristics of tissue removed. Oneor more notches or slots can be provided that extend at least partiallythrough a wall of the hollow needles. The distal end of the needles canbe tapered or pointed to facilitate insertion of the needles into thetissue. Needle tips having two or more points or prongs can be used.

According to further exemplary embodiments of the present invention, aplurality of needles can be affixed or coupled to a substrate, which canfacilitate a generation of a plurality of damaged regions using astamping mode in which the needles are inserted into the tissuesubstantially simultaneously. In other exemplary embodiments, theneedles can be provided on a roller arrangement, e.g., a cylindricalbase configured to rotate about its longitudinal axis. Such exemplaryapparatus can form a plurality of damaged regions in the tissue when theroller arrangement is rolled over the tissue surface.

The damaged regions can be holes that result from removed portions oftissue, and/or physically disrupted volumes of tissue generated byinsertion and subsequent removal of the needle(s). For example, suchdamaged regions can be generated in regular patterns or arrays, in oneor more rows, in random spatial distributions, or in other patterns.

The diameter or width of the holes or damaged tissue regions can be lessthan about 1 mm, e.g., about 0.8 mm or less, or even about 0.5 mm orless, for example, between about 0.3 mm and 0.5 mm (i.e., between about300 and 500 microns). Hollow coring needles adapted to form such holescan be formed from conventional syringe needles or the like, having asize between 18 and 30 gauge, which corresponds to internal diametersbetween about 0.84 mm and 0.14 mm. For example, needle sizes betweenabout 22 and 25 gauge (e.g., internal diameters between about 0.40 mmand 0.24 mm) can be used. Coring needles smaller than 30 gauge or largerthan 18 gauge may also be used in certain embodiments.

The fraction of tissue surface area covered by the damaged regions(e.g., the approximate areal fraction of skin tissue removed using oneor more coring needles in a treatment area) can be between about 20% andabout 70%, or between about 20% and about 50%, or between about 20% andabout 40%. Values of this areal coverage (e.g. fraction of surfacetissue removal) of between about 20-50%, for example, may beparticularly well-tolerated in skin and sufficiently large to promotedesirable cosmetic rejuvenation effects (such as increased collagenproduction and/or thickening of the dermis) while not being so large asto require extended healing times or present post-treatmentcomplications. Larger or smaller exemplary areal coverages can also begenerated in further exemplary embodiments of the present invention,e.g., to treat particular regions of skin or other tissues more or lessaggressively. A predetermined coverage can be achieved, e.g., byinserting and withdrawing one or more coring needles from a target areaof known area for a particular number of times.

In further exemplary embodiments of the present invention, one or moreneedles can be affixed to a substrate that is mechanically coupled to areciprocating arrangement. The exemplary reciprocating arrangement caninclude a motor or other actuator configured to repeatedly insert andwithdraw the one or more needles. The reciprocating arrangement can beprovided in a housing that facilitates manipulation of the apparatus,e.g., a placement of the apparatus on the tissue being treated and/ortraversing the apparatus over the tissue. The housing can optionally beconfigured to stretch or otherwise stabilize the tissue proximal to theneedle(s) being inserted, to reduce deformation of the tissue and/orimprove accuracy of the placement of the needle(s) in the tissue. Thereciprocating arrangement can further include a translational controllerconfigured to translate the needle(s) over the tissue in at least onedirection, and optionally in two orthogonal directions, to providelarger regions of treatment without translating the entire apparatusover the tissue surface.

In still further exemplary embodiments of the present invention, alow-pressure conduit can be provided in communication with the distalends of the hollow coring needles. The low pressure can create a suctionin the needles to facilitate insertion of the coring needles into tissueand/or removal of cut tissue portions from the lumen of the needles. Afilter arrangement can optionally be provided to capture the tissueportions extracted from the needles during operation. Such alow-pressure or suction arrangement can be provided in combination withany of the exemplary devices described above that are adapted to removeportions of tissue by insertion and withdrawal of one or more coringneedles.

Further exemplary embodiments of the present invention can provide acosmetic method that can improve the appearance of skin by mechanicalgeneration of fractional damage in the tissue. Such damage can begenerated by removal of small portions of tissue to generate small holesin the tissue, e.g., less than about 1 mm in width or diameter, e.g.,less than about 800 microns wide, or about 500 microns or less in width,for example, between about 300 and 500 microns in width. The depth ofthe holes can be selected based on the tissue type and location beingtreated. For example, hole depths of about 2-5 mm can be used in skintissue, where such depths correspond approximately to the thickness ofthe dermis layer. Such exemplary hole depths in skin can correspond toremoval of tissue portions extending through the entire dermis and up toand/or including the subcutaneous fat layer. Shorter and/or longerneedles can also be used. The holes can be formed by repeated insertionand withdrawal of one or more coring needles from the tissue asdescribed above. The insertions and withdrawals can be performed using amanual device containing one or more coring needles, or by using adevice that contains one or more needles coupled to a reciprocatingarrangement. A predetermined areal fraction of removed tissue can beobtained by inserting and withdrawing an apparatus containing aparticular number of coring needles, each having a particular insidediameter of a central lumen, for a particular number of times over aspecified target region to be treated.

In further exemplary embodiments of the present invention, methods andapparatuses can be provided for generating a plurality of small holes intissue by inserting and withdrawing a plurality of needles, where atleast two of the needles have a different width or diameter, length,shape, and/or other geometric characteristic. For example, one or moreneedles can be hollow, and one or more needles can be solid withprotrusions on an outer surface near the distal end. Variouscombinations of needle sizes, shapes, spacings, spatial arrangements,and geometries can be used in further exemplary embodiments.

The herein described embodiments pertain to a cosmetic method andapparatus. It shall further be noted that the herein described cosmeticmethod has been tested, and is a safe and routine procedure that can bepracticed in beauty parlors or other settings. The presented method is aminimally-invasive a method. Moreover, the exemplary method can be safeas it does not present a substantial health risk, and does not requireprofessional medical expertise to be performed. For example, noclinician is needed to perform the embodiments of the method describedherein, and no risk, much less a health risk, is presented for a personbeing treated with said cosmetic method if standard cleanliness andsterilization procedures are employed, as will become clear from thefollowing description.

Synergetic effects can arise from different combinations of the featuresand embodiments described herein, although all such combinations mightnot be described in detail. Further, it shall be noted that allembodiments of the present invention concerning the exemplary method,can be carried out with the order of the steps as described,nevertheless this has not to be the only and essential order of thesteps and/or procedures of the exemplary method. All different ordersand combinations of the method steps and/or procedures are herewithdescribed.

These and other objects, features and advantages of the presentinvention will become apparent upon reading the following detaileddescription of exemplary embodiments of the present invention, whentaken in conjunction with the appended drawings and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the present invention willbecome apparent from the following detailed description taken inconjunction with the accompanying figures showing illustrativeembodiments, results and/or features of the exemplary embodiments of thepresent invention, in which:

FIG. 1A is a schematic side view of a first apparatus for mechanicallygenerating fractional damage in tissue in accordance with exemplaryembodiments of the present invention;

FIG. 1B is a bottom view of the exemplary apparatus shown in FIG. 1A;

FIG. 2A is a schematic side view of the exemplary apparatus shown inFIG. 1A being applied to a biological tissue;

FIG. 2B is a schematic side view of a tissue portion being removed usingthe exemplary apparatus shown in FIG. 1A;

FIG. 2C is a schematic side view of a plurality of holes formed in thebiological tissue using the exemplary apparatus shown in FIG. 1A;

FIG. 3A is a schematic side view of a second apparatus for mechanicallygenerating fractional damage in tissue in accordance with furtherexemplary embodiments of the present invention;

FIG. 3B is a perspective view of the exemplary apparatus shown in FIG.3A;

FIG. 4A is a schematic side view of a third apparatus for mechanicallygenerating fractional damage in tissue in accordance with furtherexemplary embodiments of the present invention;

FIG. 4B is a schematic side view of the third apparatus shown in FIG. 4Athat is provided with a plurality of coring needles in accordance withfurther exemplary embodiments of the present invention;

FIG. 5A is a cross-sectional side view of a distal portion of a firstneedle that can be used in accordance with exemplary embodiments of thepresent invention;

FIG. 5B is a side view of a distal portion of a second needle that canbe used in accordance with exemplary embodiments of the presentinvention;

FIG. 5C is a side cross-sectional view of a distal portion of a thirdcoring needle that can be used in accordance with exemplary embodimentsof the present invention;

FIG. 5D is a side cross-sectional view of a distal portion of a fourthcoring needle that can be used in accordance with exemplary embodimentsof the present invention;

FIG. 5E is a side cross-sectional view of a distal portion of a fifthcoring needle that can be used in accordance with exemplary embodimentsof the present invention;

FIG. 6 is a schematic side view of a fourth apparatus for mechanicallygenerating fractional damage in tissue that includes a low-pressureconduit in accordance with further exemplary embodiments of the presentinvention;

FIG. 7 is an exemplary set of surface images taken at various timesshowing the appearance of fractional damage generated in porcine skinusing various needle types;

FIG. 8 is an exemplary set of cross-sectional, histologic images stainedwith masson's trichrome and taken at various times showing theappearance of fractional damage generated in porcine skin using a coringneedle as compared to an undamaged control site;

FIG. 9 is an exemplary pair of cross-sectional histologic images showinga generation of new collagen in porcine skin that was fractionallydamaged using a coring needle in accordance with further exemplaryembodiments of the present invention, as compared to an undamagedcontrol site;

FIG. 10 is a plot of exemplary data showing the observed increase inpapillary dermis thickness of porcine skin damaged with coring needlesas compared to other treated and non-treated skin areas;

FIG. 11 is a plot of exemplary data showing the observed increase inepidermal thickness of porcine skin damaged with coring needles ascompared to other treated and non-treated skin areas; and

FIG. 12 is a plot of exemplary data showing the observed increase incollagen content of porcine skin damaged with coring needles as comparedto other treated and non-treated skin areas.

Throughout the drawings, the same reference numerals and characters,unless otherwise stated, are used to denote like features, elements,components, or portions of the illustrated embodiments. Similar featuresmay thus be described by the same reference numerals, which indicate tothe skilled reader that exchanges of features between differentembodiments can be done unless otherwise explicitly stated. Moreover,while the present invention will now be described in detail withreference to the figures, it is done so in connection with theillustrative embodiments and is not limited by the particularembodiments illustrated in the figures. It is intended that changes andmodifications can be made to the described embodiments without departingfrom the true scope and spirit of the exemplary embodiments of thepresent invention as defined by the appended claims.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Exemplary embodiments of the present invention relate to and aredirected to method and apparatus for generating fractional damage intissue such as, but not limited to, skin tissue. A side view of anexemplary apparatus 100 for generating fractional damage in tissue isshown in FIG. 1A. This exemplary apparatus 100 can include one or moreneedles 120, where the needles 120 are configured to remove smallportions of tissue when they are inserted into and then withdrawn fromthe tissue. For example, the needles 120 can be hollow, e.g., such thatthey include a lumen therein. The apparatus can optionally include asubstrate 130, with the one or more needles 120 affixed or coupled tothe substrate 130. Although the substrate 130 is illustrated in FIG. 1A,certain exemplary embodiments of the present invention can be providedthat do not include such substrate 130. The substrate 130 can providemechanical stability to the one or more needles 120 and/or facilitatetheir positioning and manipulation. An optional handle 110 can beaffixed to the substrate 130 or formed as a part thereof. The substrate130 can have a substantially flat lower surface from which the needles120 protrude, or this surface can be curved or otherwise contoured,e.g., to more closely match a contour of the tissue surface. Thesubstrate can optionally be formed as part of a housing, or affixed tosuch housing, for example, where a portion of such housing may be shapedto form the handle 110.

A bottom view of the exemplary apparatus 100 is shown in FIG. 1B. Theexemplary needles 120 can be arranged in a square or rectangularpattern, as shown in FIG. 1B. Alternatively, the rows of needles 120 canbe offset or staggered, e.g., to form a triangular or hexagonal patternor the like. Other exemplary arrangements of the needles 120 can also beused, such as a random distribution of the needles 120 on the substrate130.

The exemplary apparatus 100 can be pressed onto a tissue surface, suchthat the needles 120 penetrate into the tissue 200, as shown in FIG. 2A.A plug 210 of tissue that has been separated from the surrounding tissue200 by the hollow needle 120 and located at least partially within thelumen of the needle 120 is shown in FIG. 2B. Such exemplary plugs 210can be removed from the surrounding tissue 200 when the needles 120 arewithdrawn from the tissue 200 to form a plurality of holes 220, as shownin FIG. 2C. For example, the exemplary apparatus 100 can be used as astamping tool, where the plurality of needles 120 can be inserted intothe tissue 200 once or a plurality of times in different locations. Thisexemplary “coring” procedure can facilitate a formation of a pluralityof the holes 220 in the tissue 200. The holes 220, which can be madeduring each insertion and withdrawal sequence, can have a spacingsubstantially similar to the spacing of the coring needles 120 in theapparatus 100.

The discrete holes 220 formed by the exemplary apparatus 100 can produceregions or areas of a damaged skin tissue that can elucidate a healingresponse, which can be similar to the effects produced usingconventional fractional resurfacing techniques and systems. The size ofthe holes 220 can be determined by the size of the needles 120. Forexample, the diameter of the holes 220 can correspond approximately toan inside diameter or lumen width of the needles 120, although theobserved hole diameter can be somewhat smaller after formation due tofactors such as, e.g., the malleable/elastic nature of the tissue, atendency for the gaps in the tissue to close and/or the hole wall topartially adhere to itself, and mechanical forces applied to the tissuebefore or during a formation of the holes 220. Accordingly, the diameter(size) of a hole 220 formed can generally be defined as the innerdiameter of a hollow coring needle 120 that is used to form the hole 220by cutting and removing a portion 210 of the tissue.

According to an exemplary embodiment of the present invention, thediameter or width of the holes or damaged tissue regions can be lessthan about 1 mm, e.g., about 0.8 mm or less, which can be well-toleratedby the skin. In further exemplary embodiments, the hole diameter can beabout 0.5 mm or less, which may be better-tolerated and result in afaster healing response. For example, the holes formed can be betweenabout 0.3 mm and 0.5 mm (i.e., between 300 and 500 microns).

In certain exemplary embodiments of the present invention, the coringneedle 120 can be formed, e.g., from a conventional syringe needle or anequivalent tube having a size between 18 and 30 gauge, which correspondsapproximately to internal diameters and hole sizes between about 0.84 mmand 0.14 mm. Exemplary needle sizes between about 22 and 25 gauge (e.g.,internal diameters and corresponding hole sizes between about 0.40 mmand 0.24 mm) can be used, because such needle sizes can produce holesthat are small enough to be particularly well-tolerated with a needlelarge enough to be mechanically stable and reliable when repeatedlyinserted into and withdrawn from the skin. Larger gauges (and smallerdiameters) of coring needles 120, e.g., greater than 30 gauge, can beused in certain exemplary embodiments, even though such needles mayexhibit increased flexing and/or mechanical weakness when repeatedlyinserted into and withdrawn from the tissue 200, and may also be proneto clogging. Larger needles 120 that can form correspondinglylarger-sized holes 220, e.g., needles 120 having a gauge smaller than18, can also be used for certain procedures and tissues, even thoughthey can generate more pain than smaller needles, and the larger holes220 may not be as well-tolerated, e.g., there may be an increasedlikelihood of scarring, infection, or other undesirable side effects.

Exemplary sizes of the holes 220 of about 200-500 microns can generallycorrespond to the hole sizes formed in conventional fractional surfacingprocedures, although the mechanical coring procedure described hereindoes not generate any thermal damage at the boundaries of the removedtissue portions 210. These hole sizes appear to be well-tolerated in theskin tissue, with smaller holes generally being better tolerated (e.g.,associated with faster healing times), and larger holes providing moreextensive damage that can stimulate a stronger response in the tissue.The exemplary apparatus 100 can be configured to form the holes 220having similar dimensions. Larger or smaller holes can be formed incertain tissues to achieve particular healing responses or otherphysical or biological responses.

The surface or areal fraction of the tissue damage can be determined(for a single insertion and withdrawal of the apparatus 100) by thediameters and spacings of the needles 120 provided on the substrate 130.The areal fraction of damage can be increased in a particular targetregion of tissue by applying the exemplary apparatus 100 to a pluralityof locations in the target area. For example, the fraction of tissuesurface covered by the holes 220 following an exemplary treatmentprocedure of a target area can be as small as about 0.1 (10% fractionalremoval) and as large as about 0.7 (i.e., 70% fractional removal). Ingeneral, areal fractions of holes can be between about 0.2 and 0.5, orbetween about 0.2 and 0.4. These areal coverage values may be preferablefor some procedures because they can be better tolerated, may lead toshorter local healing times, etc. Smaller or larger areal coverages canalso be generated in certain tissues, e.g., to provide a desired healingresponse or the like in the tissue.

The number of coring needles 120 provided in a substrate 130 and theirspacing can be selected based on several considerations. For example, alarger number of the needles 120 can produce a larger areal fraction ofdamage each time the exemplary apparatus 100 is inserted into andwithdrawn from the tissue. This can facilitate faster treatment of atarget area by requiring fewer insertion/withdrawal cycles for aparticular final areal coverage. However, providing a very large numberof the needles 120 in a substrate 130 can be expensive and/or presentmanufacturing challenges. Further, a larger force is needed tosimultaneously insert a large number of the needles 120 simultaneouslyinto a tissue as compared to a substrate 130 of the same dimensionscontaining a smaller number of needles. Accordingly, the number of theneedles 120 in the exemplary apparatus 100 can be between about 3 and25, or between about 6 and 20. In certain embodiments of the presentinvention, larger or smaller numbers of the needles 120 can be providedfor generating fractional damage in particular tissues and/or fortreating larger areas with fewer insertion and withdrawal cycles.

Distances between adjacent ones of the needles 120 can be less thanabout 15 mm, e.g. about 10 mm or less, or even about 5 mm or less.Smaller spacings can generate a larger fractional area of damage over asmaller area based on a single insertion of the plurality of needles 120into the tissue. Larger separation distances (e.g. greater than about 20mm) can lead to large numbers of insertion/withdrawal cycles to generatea particular areal coverage of holes 220 in the tissue being treated.Such large spacings between needles may also not be suitable fortreating relatively small target areas, e.g., having a width of about 1inch or less. Alternatively, very small separation distances between thecoring needles 120 (e.g., on the order of 3 mm or less) can be used,although such small needle spacings may present manufacturingdifficulties. It may also be more difficult to achieve a fairly uniformsurface distribution of holes 220 over larger target areas using theexemplary apparatus 100 having needles 120 that are very closely spaced.In general, the number of the needles 120 and spacings between suchneedles 120 provided in any exemplary apparatus described herein can beselected based on such factors as the size and structure of the targetregions to be treated, the desired surface coverage, speed of theprocedure (e.g., more needles 120 can facilitate fewerinsertion/withdrawal cycles to achieve a particular surface coverage),etc.

The exemplary depth of the holes 220 formed in the tissue can correspondapproximately to the length of the needles 120 protruding from a lowersurface of the substrate 130. For example, the needles 120 can extendabout 2-5 mm below the lower surface of the substrate 130. In skintissue, such coring needle protrusion lengths can facilitate theformation of the holes 220 that extend through substantially the entirethickness of the dermal layer without penetrating significantly into theunderlying subcutaneous fat layer. A penetration of the needles 120through substantially the entire dermal thickness can facilitate removalof the tissue portions 210, which can include mostly dermal tissue thatcan be more easily separated from the subcutaneous fat layer duringwithdrawal of the needles 120. In other exemplary embodiments, theneedles 120 can be configured to penetrate through the dermis and somedistance into the subcutaneous fat layer. In still further embodiments,the needles 120 can protrude at different lengths from the substrate 130in an apparatus that includes a plurality of needles. A plurality ofneedles 120 having widths that are different from one another can alsobe provided in any of the multi-needle embodiments described herein,e.g., to provide a more randomized pattern of fractional damage in thetissue.

Shallower or deeper holes 220 can be formed using the needles 120 thatare shorter or longer, respectively. The exemplary lengths and diametersof the needles 120, and the exemplary depths and widths of thecorresponding holes 220 formed, can be selected based on thecharacteristics of the tissue 200 being treated and the desired effectsto be achieved. Using the needles 120 having different characteristics(e.g., size, diameter, or geometry as described herein) can generatedesirable cosmetic effects in different tissues.

A side view of a further exemplary apparatus 300 for generatingfractional damage in tissue is shown in FIG. 3A. This exemplaryapparatus 300 can include the plurality of hollow needles 120 affixed toa cylindrical roller 330. The roller 330 can be pivotally connected to ahandle 310 such that it can rotate. A perspective view of the exemplaryapparatus 300 is shown in FIG. 3B. The needles 120 can be arranged as aplurality of rows on the roller 330, as shown in FIG. 3B. Otherarrangements of the needles 120 can also be used, such as staggered rowsor a random distribution of the needles 120 on the roller 330.

The exemplary apparatus 300 can be pressed onto a tissue surface, suchthat one or more of the needles 120 penetrates into the tissue 200. Theapparatus 300 can then be traversed over a region of tissue to betreated such that the needles 120 are forced into and then withdrawnfrom the tissue 200 as the roller 330 rolls over the tissue surface. Theexemplary apparatus 300 illustrated in FIGS. 3A and 3B is notnecessarily drawn to scale. For example, the protrusion lengths of theneedles 120 from the roller 330 may be smaller as compared to thediameter of the roller 330 than illustrated in these figures.

A further exemplary apparatus 400 in accordance with exemplaryembodiments of the present invention is shown in FIG. 4A. The exemplaryapparatus 400 can include one or more of the coring needles 120 affixedto a substrate 130, which can then be mechanically coupled to areciprocating arrangement 420 provided within a housing 430. The housing430 can also include a handle 410 to facilitate a manipulation of theexemplary apparatus 400. The reciprocating arrangement 420 can beconfigured to displace the needle 120 back and forth along a directionthat can be substantially parallel to the axis of the needle 120. Forexample, the reciprocating arrangement 420 can be powered and/oractuated by a motor or the like, controlled by a switch that can turnthe reciprocating arrangement 420 on and off, and/or further control thereciprocating frequency and/or protrusion distance of the needle 120below the lower surface of the housing 430. In a further exemplaryembodiment, the needles 120 can protrude a particular distance from thelower surface of substrate 130, and the reciprocating arrangement 420can be configured to extend and withdraw the substrate to and from aposition where the lower surface of the substrate 130 is substantiallyflush with at least a portion of the lower surface of the housing 430.In such exemplary embodiment, the protrusion distance of the needles 120can determine the depth of the holes 220 formed, rather than thecyclical position of the substrate 130 relative to the housing 430.

Another exemplary embodiment of the apparatus 400 is illustrated in FIG.4B. In this exemplary embodiment, the needles 120 are shown affixed tothe substrate 130. The various parameters, geometries, andcharacteristics of the needles 120 and the substrate 130 describedherein and/or illustrated in the figures can be used, individually or incombination, with the exemplary apparatus 400 illustrated in FIG. 4B.

The exemplary apparatus 400 of FIGS. 4A and 4B can be traversed over aregion of tissue to be treated such that the one or more needles 120forms a plurality of the holes 220 in the tissue 200 as describedherein. The exemplary depth of the holes 220 can be determined by theconfiguration of the reciprocating arrangement 420, the protrusionlengths of the needles 120, and/or the characteristics of the substrate130, as described herein. The spacing of such holes 220 in the tissuecan be determined, e.g., by the reciprocating frequency and/or thetranslational speed of the apparatus 400 over the tissue surface, andthe spacings between the needles 120 if a plurality of such needles 120are provided, as shown in FIG. 4B. For example, the exemplary apparatus400 can include a speed and/or position sensing arrangement that can beprovided in communication with the reciprocating arrangement 420 togenerate a particular spacing and/or areal fraction of the holes 220.

In further exemplary embodiments, the housing 430 can be configured tostretch skin or other tissue when the exemplary apparatus 400 is placedon the tissue to be treated. Such exemplary stretching can facilitatemechanical stabilization of the tissue, e.g., such that the one or moreneedles 120 can more easily be inserted and/or withdrawn from thetissue, while reducing or avoiding deformation of the tissue area beingtreated. Such stretching of the tissue 200 can also reduce the effectivesize of the holes 220 or other regions of damage formed by the apparatuswhen the tissue is allowed to relax after treatment. Alternatively or inaddition, the surface of the region of skin or tissue to be treated canbe stretched or stabilized using other techniques prior to and/or duringtreatment of the region in accordance with any of the exemplaryembodiments described herein.

In another exemplary embodiment, the reciprocating arrangement 420 canfurther include a translational mechanism configured to translate theone or more of the needles 120 over the surface of the tissue 200 in oneor two orthogonal directions or a combination thereof. For example, thereciprocating arrangement 420 can be configured to translate such one ormore of the needles 120 over a portion of the tissue surface, while theexemplary apparatus 400 is held stationary with respect to the tissuesurface. In one exemplary embodiment, the reciprocating arrangement 420can be configured to translate the one or more needles 120 along asingle direction to form one or more rows of the holes 220 or damagedregions. The exemplary apparatus 400 can optionally be translated overthe tissue surface after such rows are formed to generate a plurality ofsuch holes 220 over a larger region of the tissue.

In further exemplary embodiments of the present invention, any of theexemplary apparatuses described herein can be configured to generate theholes 220 in any of a variety of spatial distributions in the tissuebeing treated. For example, the holes 220 can be formed as one or morerows, a regular two-dimensional pattern (such as a square, rectangular,or triangular array), a random distribution, or the like. Such patternsor spatial distributions of holes 220 can be generated based on, e.g.,the exemplary configuration of one or more of the provided needles 120in the substrate 130, the properties of the reciprocating arrangement420, and/or the rate of translation of the exemplary apparatus 400 overthe surface of the tissue 200.

A cross-sectional side view of a distal portion of an exemplary needle120 is shown in FIG. 5. The distal end 500 of the needle 120 can beprovided with a sharpened edge to facilitate penetration of the needle120 into the tissue 200 being treated. One or more protrusions 510 canoptionally be provided within the lumen, e.g., along an inner surface ofthe needle 120. Such protrusions 510 can facilitate a removal of thetissue plugs 210 that can be present within the needle 120 when it isinserted into the tissue 200 as described herein. For example, suchprotrusions 510 can be angled upward as shown in FIG. 5 to facilitatethe needle 120 to penetrate the tissue 200 easily. These protrusions 510can then grab onto the tissue plug 210 in a barb-like manner to pull theplug 210 from the surrounding tissue 200 when the needle 120 iswithdrawn. The plugs 210 that are removed and reside within the needle120 can be pushed upward towards the proximal end of the needle 120 bysubsequent plugs 210 formed by successive insertions of the needle 120into the tissue 200.

Another exemplary configuration for the distal end of a coring needle120 is shown in FIG. 5B. The distal end of the needle 120 can beprovided with a single point or prong 550, similar to that of aconventional Chiba needle, or with two or more points or prongs 550,e.g., in a configuration similar to that of the outer cannula of aconventional Franseen needle or crown-point tip. For example, suchprongs 550 can be formed by a planar grinding of the end portion of ahollow tube at acute angles relative to the longitudinal axis of thetube, at one or more angular intervals around the longitudinal axis. Forexample, a 2-pronged needle end, such as illustrated in FIG. 5B, can beformed by grinding the opposite sides of a hollow tube or needle (e.g.,orientations that are 180 degrees apart) in a plane that forms an acuteangle with the longitudinal axis of the tube. Similarly, a 3-prongedneedle can be formed by angular grinding of the needle at 120 degreeintervals; 4-pronged needles can be formed by grinding at 90 degreeintervals, etc. Such prongs 550 can facilitate the insertion of theneedle 120 into the tissue 200, and can further facilitate detachmentand removal of tissue portions 210 upon the withdrawal of the needle 120from the tissue 200.

Other exemplary configurations of one or more of the needles 120 can beused with any of the various exemplary embodiments described herein. Forexample, another needle 120 as shown in a cross-section in FIG. 5C canbe used, which includes one or more angled notches 560 provided in theneedle walls, e.g., near the distal end of the needle 120. Suchexemplary notches 560 can extend partially or completely through a wallof the exemplary hollow needle 120. During the insertion and/orwithdrawal of the needle 120, such notches 560 can be adapted to cutinto the tissue adjacent to the needle 120, thereby removing a portionof the tissue and generating a hole or gap. For example, the notches 560can be angled upward (as shown in FIG. 5C) and/or downward relative tothe distal end of the needle 120.

In further exemplary embodiments, an edge 565 of the notches 560 canoptionally protrude from the outer periphery of the needle wall, asshown in cross section in FIG. 5D. The protruding edge 565 can provide acutting edge or the like, which may be viewed as analogous to theconfiguration and operation of some cheese graters but on a smallerscale, to facilitate separation and removal of a portion of the tissueproximal to the needle 120 as it is moved through the tissue.

In further exemplary embodiments, one or more of the needles 120 can beprovided as a solid non-hollow needle 520 that includes one or moreextensions 570 protruding from a lateral side thereof, e.g., as shown inan exemplary cross-sectional view in FIG. 5E. If more than one suchextension 570 is provided, they can be distributed at various angularintervals around the axis of the needle 520. The extensions 570 canextend over any one of various lengths along the axis of the solidneedle 520, and can be located near the distal end of the needle 520.These extensions 570 can be provided with a size and shape that isstructured or adapted to remove small portions of tissue when the needle520 is inserted into and/or withdrawn from the tissue being treated. Forexample, the extensions 570 can be similar in shape to the protrusions510 shown in FIG. 5A, with the extensions 570 provided on an outersurface of the solid needle 520 rather than on an inner surface of ahollow needle 120 as shown in FIG. 5A. Preferably, the outer diameter ofthe extensions 570 around the longitudinal axis of the needle 520 can beless than about 1 mm, and optionally less than about 0.5 mm. Such smallsizes can limit the size of the damaged regions of tissue generated, andthereby reduce or prevent formation of visible markings or scars in thedamaged tissue.

The exemplary illustrations of the needles 120, 520 shown in FIGS. 5A-SEare not necessarily drawn to scale. For example, the sizes of aprotrusion 510, a notch 560, and/or an extension 570 relative to theneedle width or diameter, and/or their distances from the needle tip,can vary from what is shown in the illustrations. The specific shapes ofthese features and, e.g., the notch edges 565, can also vary from thoseshown in the drawings. Further, different ones of the needles 120, 520can be provided with different diameters, feature sizes, and or lengthsin a single apparatus 100, 200, 400, 600.

In still further exemplary embodiments, one or more extensions 570 canbe provided on an outer wall or surface of any of the hollow coringneedles 120 described herein. In yet further exemplary embodiments, asingle exemplary apparatus 100, 300, 400, 600 can be provided with aplurality of needles 120, 520, where one or more of such needles 120,520 can be provided with different ones of the features illustrated inFIGS. 5A-5E and described herein.

In further exemplary embodiments of the present invention, the exemplaryapparatus 100, 300, 400 can be provided with suction or low pressure toimprove the ease of needle insertion and facilitate removal of tissueportions 210 from the needle upon withdrawal from the tissue 200. Anexemplary apparatus 600 that includes one or more coring needles 120, asubstrate 130, and a low-pressure conduit 620 is illustrated in FIG. 6.The conduit 620 is provided in communication with a proximal end of thecoring needles 620. The conduit 620 can also be connected to a source oflow pressure (not shown) such as, e.g., a vacuum pump, apartially-evacuated vessel or container, a piston, another vacuumsource, or the like. The low pressure in the conduit 620 can generate asuction in the needles 120, which can facilitate insertion of theneedles 120 into tissue 200 being treated, extraction of tissue portions210 from the surrounding tissue 200, and/or removal of such tissueportions 210 from the lumen of the needles 120 after the needles 120 arewithdrawn from the tissue 200.

The exemplary apparatus 600 can optionally include a valve, restriction,and/or other pressure arrangement between the low pressure source andthe proximal ends of the needles 120, where the pressure arrangement isadapted to control the degree of suction or low pressure present in theconduit. In an alternative exemplary embodiment, characteristics of thelow pressure source can be controlled directly to vary the pressure inthe conduit 620.

An optional filter arrangement 630 can be provided in the exemplaryapparatus 600, e.g., between the proximal end of the needles 120 and thelow-pressure source. For example, the filter arrangement 630 can beprovided at a location in the conduit 620 as illustrated in FIG. 6. Thefilter arrangement 630 can include a polymer or metal mesh or screen, apaper filter, or the like adapted to capture tissue portions 210 thatmay be sucked out of the needles 120 during operation of the apparatus600. The filter arrangement 630 can include a filter element that can beeasily cleaned or discarded during or after operation of the exemplaryapparatus 600. The filter arrangement 630 is preferably sized so that itwill not become clogged with captured tissue portions 210 duringoperation, which may reduce or eliminate the suction provided to theneedles 120. An optional reservoir or container (not shown) can beprovided and adapted to store tissue portions 210 that are trapped bythe filter arrangement 630, where such tissue portions 210 can bedirected into the container or fall into it under the influence ofgravity, and can then be removed from the exemplary apparatus 600 anddiscarded.

The low-pressure conduit 620 and optional filter arrangement 630 asdescribed above can be combined with any of the exemplary embodimentsdescribed herein, including the exemplary devices 100, 400 shown inFIGS. 1 and 4. The advantages of such a combination can include, e.g.,easier insertion of the needles 120 into tissue 200 being treated, moreeffective removal of tissue portions 210 from the central lumen ofneedles 120 during operation of the devices, reduced clogging of theneedles 120, etc.

In further exemplary embodiments of the present invention, a method isprovided that allows for the removal of small portions of aged ordamaged skin, which can facilitate and/or promote the growth of new skincomponents while reducing or avoiding undesirable side effects such asscarring, infection, and the like.

Further exemplary embodiments of the present invention provide acosmetic method that can improve the appearance of skin by mechanicalgeneration of fractional damage in the tissue. Such damage can begenerated by removal of portions of tissue to generate small holes inthe tissue. A width or diameter of these holes can be, e.g., less thanabout 1 mm, or less than about 0.5 mm, e.g., between about 0.3 mm andabout 0.5 mm, as described herein above.

The depth of the holes can be selected based on the tissue type andlocation being treated. For example, hole depths of about 2-5 mm can beused in skin tissue, where such depths correspond approximately to thethickness of the dermis layer. Such hole depths in skin can correspondto removal of tissue portions extending through the entire dermis and upto the subcutaneous fat layer. In further exemplary embodiments, longerneedles 120, 520 can be provided that can extend into the subcutaneousfat layer when inserted partially or fully into skin tissue.

Tissue portions can be removed, and holes can be formed, by repeatedinsertion and withdrawal of one or more needles 120, 520 from the tissueas described herein above. The insertions and withdrawals can beperformed using a manual device containing one or more needles 120, 520,or alternatively by using a device that contains one or more needles120, 520 coupled to a reciprocating arrangement 420. A predeterminedareal fraction of removed tissue can be obtained by inserting andwithdrawing a particular number of needles 120, 520 for a particularnumber of times over a specified target region to be treated.

In further exemplary embodiments of the present invention, a source ofpressurized fluid, e.g. saline or the like, can be coupled to the lumenof the hollow coring needle 120. The flow of such fluid can becontrolled using conventional means, and used to clean or flush outtissue portions and/or other debris that may be present in the lumen. Instill further embodiments, a heat source, e.g., a resistive heater orcurrent, can be provided in communication with one or more of theneedles 120, 520, and adapted to cauterize, ablate, or otherwise removetissue or other residue that may adhere to the needles 120, 520.

As suggested by the observations described below, the method ofmechanically generating fractional damage in skin tissue by removingsmall tissue portions, e.g., by repeatedly inserting and withdrawing oneor more coring needles, appears to be safe and well-tolerated by theskin, with little risk of infection or unwanted side effects as comparedwith laser-based resurfacing procedures. Such methods can stimulatecollagen formation in skin and lead to an increase in dermal andepidermal thickness, which can improve the appearance of aged orphoto-damaged skin.

Example

A large-animal study of the method and apparatus according to certainexemplary embodiments of the present invention was performed. Tissuecoring needles were produced by modifying conventional hypodermicneedles, so that a cylindrical area of tissue is removed when theypuncture the skin and are then withdrawn, similar to a core biopsy buton a smaller size scale. Standard 25 gauge hypodermic needles (e.g.,Becton Dickinson, Franklin Lakes, N.J.), having a 260 micron innerdiameter, were ground down such that their anti-beveled edges wereremoved, to form hollow needles having a double-crown or double-prongedtip, such as that illustrated in FIG. 5B. Devices were prepared inaccordance with embodiments of the present invention that include foursuch coring needles affixed in a 2×2×4 cm block of rubber. The needleswere provided in a square array, with 8 mm of separation between theneedles along the sides of the square, and with the distal ends of theneedles extending 4 mm from the lower surface of the rubber block. Forcomparison, several similar 4-needle devices were prepared usingdifferent types of needles. Devices were assembled with four standard or“regular” 25 gauge hypodermic needles (not having double-pronged groundtips), four regular 23 gauge needles, four “solid” 25 gauge needles(having the same outer diameter but without a hollow center) and four 23gauge coring (double-pronged) needles. These additional devices werealso tested as described herein.

One female miniature swine (Sus scofa domesticus), 1½ years of age andweighing 117 kg, was utilized for this study. The pig was subjected togeneral anesthesia and positioned on its right side. The hair from theleft flank was clipped and the skin was prepped with soap. The pig wasgiven a single dose of buprenorphine (0.01 mg/kg) for analgesia, andthen draped in a sterile fashion.

Using a template, the corners of 32 1-inch treatment squares were markedby tattoo. A total of 24 squares were treated with the devicescontaining either standard (“regular”) 25 gauge hypodermic needles,solid 25 gauge needles, or 23 or 25 gauge coring needles. The deviceused for each treatment square was repeatedly pressed onto the square ofskin tissue by hand and removed for a prescribed number of times, withthe device being randomly translated within the area of the square beingtreated before each re-insertion. The number of insertions/removals foreach site was calculated to provide an areal fraction of affected tissue(based on the ID of the needles) of either 0.20 (20% coverage) or 0.40(40% coverage). For example, a coverage of 20% corresponds to about 625insertion/withdrawal cycles per square inch with a device containingfour 25 gauge needles, and a coverage of 40% corresponds to about 1250insertion/withdrawal cycles of the same device per square inch.Coverages of 20% and 40% can also be achieved with about 362 and 724insertion/withdrawal cycles per square inch, respectively, of a devicehaving four 23 gauge needles. Eight marked squares were left untreatedas controls. Devices containing new needles were used for each treatmentsite.

At the completion of the coring procedure, 4 mm punch biopsies wereobtained from each treatment and control site. These biopsy sites werethen each closed with a single, 3-0 nylon suture. The wounds were thendressed with triple antibiotic ointment, zeroform, gauze and tape.

This entire procedure was then repeated on the opposite (right) flank,and photographs were taken of the treatment and control squares on thisside both before and after the needle devices were applied to thevarious treatment sites. On days 7, 28, 56, and 84 (1, 4, 8, and 12weeks, respectively) after the initial coring procedures were performed,the pig was again placed under general anesthesia and further biopsiesfrom sites on the left flank, and pictures of the sites on the rightflank, were taken.

Four series of photographs of certain treatment squares of pig skintissue are presented in FIG. 7. Pictures in row A were taken of acontrol square that was not penetrated by any needles; pictures in row Bwere taken of a control square treated with regular (conventional) 25gauge hypodermic needles; pictures in row C were taken of a controlsquare treated with solid 25 gauge needles; and pictures in row D weretaken of a control square treated with 25 gauge coring needles having2-prong tips configured to remove a portion of the tissue upon beingwithdrawn. Pictures in the first and second columns of FIG. 7 were takenimmediately pre- and post-needle treatment. Pictures in the third,fourth, and fifth columns of FIG. 7 were taken at 1, 4, and 12 weeksafter the needle treatment, respectively. These photographs were takenusing a Nikon D3100 digital SLR with a Nikkon Micro-Nikkor 105 mm MacroLens (Nikon Corporation, Tokyo, Japan). Image measurements were madeusing Adobe Photoshop CS4 (Adobe Systems Incorporated, San Jose,Calif.). The surface coverage for each treated square shown in FIG. 7was about 20%.

The micro-coring needle apparatus and technique in accordance withembodiments of the present invention appeared to be well-tolerated. Alltreatment areas were observed immediately post-treatment to becharacterized by redness and serous exudates (second column of FIG. 7).This initial appearance is similar to that observed with some laserresurfacing procedures. However, the treated sites healed quickly, withany observable erythema resolved within two weeks of the treatment. By 4weeks (fourth column in FIG. 7), the treatment sites appeared to becompletely healed. The sites treated with solid needles at 40% coverageappeared to be the last to heal. There was no evidence of infection orscarring at any of the 64 treatment sites over the 12-week study.

Punch biopsies from the treated sites were fixed with 10% formalin,embedded in paraffin and cut into 5 μm sections. The sections werestained with hematoxylin and eosin, Masson's Trichrome, and Verhoeff-VanGieson. Images of the sectioned and stained biopsies were acquired on aNikon Eclipse E600 microscope in brightfield (Nikon). A series of fourbiopsy images with Masson's Trichrome staining for an untreated controlsite, taken at 0, 1, 4, and 8 weeks after treatment of the other sitesare show in FIGS. 8A-8D. The images in FIGS. 8E-8H were taken of stainedbiopsies from a site treated with 25 gauge coring needles, as describedabove, at these same time intervals of 0, 1, 4, and 8 weeks aftertreatment of the site. The length of the scale bar in these images is100 microns.

Histologically, the areas of tissue coring/removal after treatment withthe coring needles were easily detectable and were approximately 200-300microns in diameters and about 600-700 microns in depth. (See FIG. 8E.)All of the treatment sites exhibited re-epithelialization by one week ofelapsed time after treatment, as shown in FIG. 8F. The coring sitesexhibited enhanced undulating rete ridges, which increases theepidermal-dermal junction interface as shown in FIGS. 8F-H, as comparedto the control (untreated) area shown in FIGS. 8A-D. These treated sitesalso had a thicker papillary dermis, most notably visible 4 weeks aftertreatment as shown in FIG. 8G. This region contained numerousfibroblasts, which are the cells responsible for new collagen andelastin synthesis.

After 8 or more weeks post-treatment (see FIG. 8H), the coring sitesappeared to return to a more normal skin architecture, similar to thecontrol sites shown in FIGS. 8A-D. This observation is not surprising,because the porcine skin that was treated was not aged but healthy.Further, porcine skin tissue does not exhibit human-like wrinkles,photodamage, or similar skin vasculature, so a “cosmetically” improvedappearance of the pig skin would not be expected.

However, there is histologic evidence that some rejuvenation andremodeling occurred. The images shown in FIGS. 9A and 9B are the biopsysamples of an untreated control site and one treated with 25 gaugecoring needles, respectively, that were stained for elastin 8 weeksafter treatment. The arrows in FIG. 9B indicate a significant increasein the number and desirable orientation of elastin fibers. The length ofthe scale bar in FIGS. 9A and 9B is 100 microns. Elastin staining at 8and 12 weeks after treatment of a site with coring needles revealedbeading of the elastic fibers, indicating that new elastin was beinglaid down. These elastin fibers are newly aligned in a horizontalfashion, a configuration that has been observed after fractional lasertreatment and which is thought to contribute to traction stress and skintightening. This significant rejuvenation behavior was not observed tothe same extent in control sites, nor in sites treated with the solidand regular hypodermic needle types (not shown).

Whereas the significance of new, healthy fibroblast and collagen iswell-documented in skin rejuvenation models, the role of elastin is lessclear. Although elastin makes up a small percent of dermal connectivetissue, it is clearly important, as the lack of elastin in conditionssuch as Ehlers-Danlos has a dramatic presentation. Studies havedemonstrated objective increases in the amount of elastin after variousskin rejuvenation procedures, although there is minimal correlation ofthis with skin tightening. It has been suggested that a horizontalrealignment of elastin may lead to skin tightening rather than anincrease in density. The production of new elastin in tissue sitestreated with coring needles, in accordance with embodiments of thepresent invention, did appear to form longer and more horizontallyopposed fibers as compared to the randomly distributed fibers found inthe control tissues, as shown in FIG. 9.

While all three needle types investigated (solid, regular hypodermic,and coring) appeared to induce some element of skin remodeling whencompared to the untreated controls, the results of the coring needleswere most profound. FIG. 10 shows a graph of measured papillary dermisthickness in biopsy samples for a control (untreated) site and for sitestreated with the three types of needles, 4 weeks after treatment of theskin sites. The papillary dermis of the sites treated with coringneedles was observed to be up to 196% thicker at this time as comparedto the untreated control sites (p<0.01). Multiple group comparisons weremade by ANOVA using the Tukey-Kramer post hoc analysis. A p-value ofless than 0.05 was considered statistically significant. Data analysiswas performed using the GraphPad Prism statistical software (GraphPadInc, San Diego, Calif.). The vertical error bars in FIG. 10 represent asingle standard deviation and (*) indicates p<0.05, (**) indicatesp<0.01, and (***) indicates p<0.001, as a statistical significance levelbetween the groups within the horizontal bars in this figure.

The observed increase in thickness of the papillary dermis in skin areastreated with coring needles may be significant with respect to cosmeticrejuvenation effects. Expansion of this zone has been correlated withtreatment depth and skin contracture. For example, more aggressiveresurfacing therapies (e.g., high-flux laser and dermabrasion) have beenobserved to result in a thicker papillary dermis at two months. Retinoicacid treatment can increase the thickness and production of collagen inthe papillary dermis by 80%. The importance of the papillary dermis inskin rejuvenation may result from the specialized cells it contains.Papillary fibroblasts have been found to to be a distinct population,which are more significantly impacted by aging than their deeper,reticular conterparts. Papillary fibroblasts were observed to have ahigher capacity to sustain kertinopoiesis and promote epidermalmorphogenesis. It is well known that the vasculature of the papillarydermis supplies the epidermis; however, it appears that a robust supplyof papillary fibroblasts may be needed to maintain a youthful-appearingdermal-epidermal junction and the epidermis itself. The present exampleof skin sites treated with coring needles as described herein hasdemonstrated a significant amount of cellular activity within thisregion.

In addition to a younger-appearing rete ridge pattern and a thickersuperficial dermis, the skin sites treated with coring needles exhibiteda thicker epidermis at 4 weeks after treatment. A graph of epidermalthickness in biopsy samples for a control (untreated) site and for sitestreated with the three types of needles, measured 4 weeks aftertreatment of the sites as described herein, is shown in FIG. 11. Theepidermis of the sites treated with the coring needles appear to besignificantly thicker (187%) than the control sites (p<0.01) in thisfigure.

Collagen content for each treatment site was assessed at 12 weeks afterthe treatment of the various skin sites with the needle devices. 4 mmpunch biopsies were digested in a solution of 10 ml of 0.5M acetic acidand Pepsin 0.1 mg/ml (Sigma Aldrich, St. Louis, Mo.) overnight at 4° C.Samples were homogenized using a TissueRuptor (Quiagen, Hilden,Germany). The protocol for the Sircol Soluble Collagen Assay (Biocolor,Carrickfergus, UK) was then followed using a 1/1000 initial dilution.Absorbance was determined using a Spectramax M2 microplate reader(Molecular Devices, Sunnyvale, Calif.).

A plot of the measured collagen content in control (untreated) sites andin sites treated with the three types of needles, 12 weeks aftertreatment of the skin sites, is shown in FIG. 12. In total, the sitestreated with coring needles had a mean collagen content that was 89%higher than that of the control (untreated) sites (P<0.001). Thisaverage collagen level was also significantly higher than that measuredin sites treated with either the regular hypodermic needles or the solidneedles, as shown in FIG. 12.

The collagen assay results are consistent with observation ofsignificant collagen neogenesis around the regions of skin that wereremoved with the coring needles. This collagen production was alsoobserved to a lesser extent in tissue treated with the solid needles.The production of new collagen has been correlated with a clinicalimprovement of aged or photo-aged skin. The creation of new, fine,compact collagen has been observed in numerous laser studies and may bemost important hallmark of skin rejuvenation. An 89% increase incollagen content was detected by ELISA techniques, 12 weeks aftertreatment, in the sites treated with coring as compared to the control(untreated) sites.

In summary, an exemplary embodiment of method and apparatus has beentested that includes mechanical removal of small columns of skin tissueusing one or more coring needles as described herein. Immediatelyfollowing the removal of multiple small tissue cores from a skin site,erythema and serous oozing were observed that is substantially similarto that observed after generating a similar density of piercings withsimilarly-sized solid (non-coring) needles. The erythema generated bythe coring devices and procedures described herein is also similar tothat observed following a high-density laser fractional resurfacingtreatment. However, the coring sites were observed to be quicklyre-epithelialized and return to normal skin coloration within one week,which can result in part from the minor degree and distributed geometryof epidermal damage.

The exemplary results indicate that significant amounts of tissue can beremoved with coring needles, without creating scar or leading to anyother adverse advent. For example, embodiments of the present inventioncan provide cleanly cored tracts that lead to changes in skinarchitecture and collagen content, with no observable cellularinfiltrate or significant inflammation. Despite an observed increase infibroblast activity and collagen neogenesis at one week and one monthafter treatment, the cored skin contained only scattered macrophages andlymphocytes. In contrast, fractional ablative lasers tend to produce avigorous inflammatory response and a neutrophilic infiltrate around thenecrotic channels in both humans and pigs with a coagulation zone thatreaches about 65 microns in thickness, as well as increased infiltrate,micro thrombosis and sclerosis of vessel walls when using moderate laserflux. having been observed for greater than 6 months after fractionallaser treatment. Further, the lack of inflammation or expression of heatshock proteins following procedures according to embodiments of thepresent invention may lead to a more rapid recovery and decreasedadverse effects as compared to conventional laser-based resurfacingprocedures.

Although commonly employed as a large animal model for skinrejuvenation, the pig is a poor comparison to humans, as they do notexhibit human like wrinkles, photodamage or similar skin vasculature.The test pig had neither aged nor lax skin, thus there was little chancefor us to demonstrate any gross improvement in texture over ouruntreated sites.

The needle-based rejuvenation procedure described herein was welltolerated, with none of the treatment sites showing any sign ofinfection or scar. The sites healed quickly, with re-epithelializationwithin 1 week and resolution of erythema by 2 weeks after treatment.Sites treated with coring needles exhibited significant thickening ofthe papillary dermis and epidermis, as well as enhanced undulating reteridges increasing the epidermal-dermal junction—a sign of youthful skin.These sites also exhibited newly aligned and augmented elastic fibersand a significant increase in collagen content as compared to untreatedsites.

The coring needle-based skin rejuvenation method and apparatus asdescribed herein was observed to be safe and effective for inducing themicroscopic and biologic endpoints of skin rejuvenation, and moreeffective than similar procedures and devices that use other needletypes. Accordingly, embodiments of the present invention can provide anew modality for the safe and cost-effective treatment of age-relatedrhytides, skin laxity, photo damage, scarring and striae.

The foregoing merely illustrates the principles of the presentinvention. Other variations to the disclosed embodiments can beunderstood and effected by those skilled in the art in practising theclaimed invention from a study of the drawings, the disclosure, and theappended claims. In the claims, the word “comprising” does not excludeother elements or steps and the indefinite article “a” or “an” does notexclude a plurality. The mere fact that certain measures are recited inmutually different dependent claims does not indicate that a combinationof these measures cannot be used advantageously. Any reference signs inthe claims should not be construed as limiting the scope of the claims.Various modifications and alterations to the described embodiments willbe apparent to those skilled in the art in view of the teachings herein.It will thus be appreciated that those skilled in the art will be ableto devise numerous techniques which, although not explicitly describedherein, embody the principles of the present invention and are thuswithin the spirit and scope of the present invention. All referencescited herein are incorporated herein by reference in their entireties.

1-41. (canceled)
 42. An apparatus for producing a cosmetic effect in askin tissue, comprising: at least one hollow needle comprising a distalend thereof, wherein the at least one hollow needle is configured toremove portions of the skin tissue when the hollow needle is repeatedlyinserted into and withdrawn from the skin tissue, so as to produce thecosmetic effect, and wherein: (i) the apparatus is configured to removean areal fraction of the skin tissue that is about 0.1; or (ii) theapparatus further comprises: a) a filter arrangement and container forcapturing the portions of the skin tissue to be discarded; or b) areciprocating arrangement configured to translate the hollow needle overthe skin tissue in one direction or two orthogonal directions.
 43. Theapparatus of claim 42, wherein the at least one hollow needle comprisesone, two, or three or more prongs at the distal end of the hollowneedle.
 44. The apparatus of claim 43, wherein the apparatus comprises aplurality of hollow needles.
 45. The apparatus of claim 44, whereinadjacent hollow needles of the apparatus have a distance of: (i) about15 mm or less; or (ii) about 10 mm or less; or (iii) about 5 mm or less.46. The apparatus of claim 42, wherein the at least one hollow needle:(a) has an inner diameter of: (i) less than about 0.5 mm; or (ii)between about 0.24 mm and 0.4 mm; or (iii) between about 0.3 mm and 0.5mm, or (b) has a gauge size between about 22 and 25, or (c) has a lengthbetween about 2 mm and about 5 mm, or (d) is configured to extendthrough the entire dermis to at least a depth of a subcutaneous fatlayer.
 47. The apparatus of claim 42, wherein the at least one hollowneedle comprises a lumen and at least one protrusion provided within thelumen, optionally, wherein the protrusion is angled upward and isconfigured to grab onto and pull the portion of the skin tissue from thesurrounding skin tissue when the at least one hollow needle is withdrawnfrom the skin tissue.
 48. The apparatus of claim 42, wherein the atleast one hollow needle further comprises at least one angled notchprovided in a wall of the hollow needle, optionally, wherein an edge ofthe at least one angled notch protrudes outward beyond an outerperiphery of the at least one hollow needle.
 49. The apparatus of claim42, wherein the distal end of the at least one hollow needle comprises asharpened edge and wherein the sharpened edge is configured tofacilitate insertion of the hollow needle into the skin tissue.
 50. Theapparatus of claim 42, wherein the reciprocating arrangement: (i) isconfigured to displace the at least one hollow needle back and forthalong a direction substantially parallel to the axis of the hollowneedle; or (ii) comprises a motor, an actuator, or both; or (iii) isenclosed in a housing.
 51. The apparatus of claim 50, wherein thehousing is configured to stretch or stabilize the skin tissue proximalto the at least one hollow needle, to reduce deformation of the skintissue, or to improve accuracy of the insertion of the at least onehollow needle into the skin tissue.
 52. The apparatus of claim 42,further comprising one or more of the following: (i) a substrate,wherein the at least one hollow needle is coupled to the substrate; or(ii) a handle; or (iii) a speed sensing arrangement, wherein the speedsensing arrangement is configured to control a reciprocating frequencyof the at least one hollow needle; or (iv) a position sensingarrangement, wherein the position sensing arrangement is configured tocontrol the insertion position of the at least one hollow needle intothe skin tissue; or (v) a low-pressure conduit, wherein the low-pressureconduit is connected to a low pressure source to generate a suction inthe at least one hollow needle, optionally, wherein the low-pressuresource is a vacuum pump or a piston; or (vi) a heat source, wherein theheat source is connected to the at least one hollow needle and isconfigured to remove portions of the skin tissue from the hollow needle,optionally, wherein the heat source is a resistive heater or current; or(vii) a source of pressurized fluid, wherein the pressurized fluid isconnected to the at least one hollow needle and is configured to cleanor flush out portions of the skin tissue from the hollow needle,optionally, wherein the pressurized fluid is saline.
 53. The apparatusof claim 52, wherein the substrate: (i) is configured to repeatedlyinsert and withdraw the at least one hollow needle from the skin tissuein a stamping mode; or (ii) comprises a flat or curved lower surface,wherein the lower surface is configured to match a contour of the skintissue, and optionally, wherein the at least one hollow needle isconfigured to extend between about 2 mm and 5 mm below the lower surfaceof the substrate; or (iii) is substantially cylindrical and configuredto roll over a surface of the skin tissue.
 54. The apparatus of claim52, wherein the low pressure conduit is configured to facilitateinsertion of the at least one hollow needle into the skin tissue orremoval of portions of the skin tissue from the hollow needle.
 55. Theapparatus of claim 42, wherein the apparatus is programmed to produce anarray pattern in the skin tissue by removing the portions of the skintissue, optionally, wherein the array pattern comprises one or morerows, a two-dimensional pattern, or a random distribution, optionally,wherein the two-dimensional pattern is a square, rectangle, triangle, orhexagon.
 56. A method for removing aged or damaged skin tissue,comprising: producing a plurality of holes in the skin tissue byremoving portions of the skin tissue using the apparatus of claim 42,and discarding the removed portions of the skin tissue, wherein themethod promotes the growth of new skin components or reduces scarring,age-related rhytides, skin laxity, photo damage, or striae.
 57. Themethod of claim 56, wherein an areal fraction of about 0.1 of the skintissue is removed.
 58. The method of claim 56, wherein the at least onehole has a depth: (i) between about 2 mm and about 5 mm; or (ii) thatextends through the entire dermis to at least a depth of a subcutaneousfat layer.
 59. The method of claim 56, wherein the at least one hole hasa diameter: (i) less than about 0.5 mm; or (ii) between about 0.24 mmand 0.4 mm; or (iii) between about 0.3 mm and 0.5 mm.
 60. The method ofclaim 56, wherein the adjacent holes formed by the apparatus have adistance of: (i) about 15 mm or less; or (ii) about 10 mm or less; or(iii) about 5 mm or less.
 61. The method of claim 56, wherein theplurality of holes in the skin tissue produce an array pattern,optionally, wherein the array pattern comprises one or more rows, atwo-dimensional pattern, or a random distribution, optionally, whereinthe two-dimensional pattern is a square, rectangle, triangle, orhexagon.